Linked Life Data

19254700

Source:http://linkedlifedata.com/resource/pubmed/id/19254700

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2009-4-6
pubmed:abstractText
A mutation in the Vps33a gene causes Hermansky-Pudlak Syndrome (HPS)-like-symptoms in the buff (bf) mouse mutant. The encoded product, Vps33a, is a member of the Sec1 and Class C multi-protein complex that regulates vesicle trafficking to specialized lysosome-related organelles. As Sec1 signaling pathways have been implicated in pre-synaptic function, we examined brain size, cerebellar cell number and the behavioral phenotype of bf mutants. Standardized behavioral tests (SHIRPA protocols) demonstrated significant motor deficits (e.g., grip strength, righting reflex and touch escape) in bf mutants, worsening with age. Histological examination of brain revealed significant Purkinje cell loss that was confirmed with staining for calbindin, a calcium binding protein enriched in Purkinje cells. This pathologic finding was progressive, as older bf mutants (13-14 months) showed a greater attrition of neurons, with their cerebella appearing to be particularly reduced (approximately 30%) in size relative to those of age-matched-control cohorts. These studies suggest that loss of Purkinje neurons is the most obvious neurological atrophy in the bf mutant, a structural change that generates motor coordination deficits and impaired postural phenotypes. It is conceivable therefore that death of cerebellar cells may also be a clinical feature of HPS patients, a pathological event which has not been reported in the literature. In general, the bf mutant may be a potentially new and useful model for understanding Purkinje cell development and function.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1872-6240
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
1266
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18-28
pubmed:meshHeading
pubmed-meshheading:19254700-Aging, pubmed-meshheading:19254700-Animals, pubmed-meshheading:19254700-Brain, pubmed-meshheading:19254700-Calcium-Binding Protein, Vitamin D-Dependent, pubmed-meshheading:19254700-Cell Death, pubmed-meshheading:19254700-Cerebellum, pubmed-meshheading:19254700-Glial Fibrillary Acidic Protein, pubmed-meshheading:19254700-Hand Strength, pubmed-meshheading:19254700-Hermanski-Pudlak Syndrome, pubmed-meshheading:19254700-Immunohistochemistry, pubmed-meshheading:19254700-Magnetic Resonance Imaging, pubmed-meshheading:19254700-Mice, pubmed-meshheading:19254700-Mice, Inbred C57BL, pubmed-meshheading:19254700-Mice, Mutant Strains, pubmed-meshheading:19254700-Motor Activity, pubmed-meshheading:19254700-Organ Size, pubmed-meshheading:19254700-Posture, pubmed-meshheading:19254700-Purkinje Cells, pubmed-meshheading:19254700-Startle Reaction, pubmed-meshheading:19254700-Vesicular Transport Proteins
pubmed:year
2009
pubmed:articleTitle
The Vps33a gene regulates behavior and cerebellar Purkinje cell number.
pubmed:affiliation
Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY, USA. sreenivasulu.chintala@roswellpark.org
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural